Active pharmaceutical ingredients are frequently delivered to the patient in, for example, a solid-state as part of an approved dosage form. These active ingredients can exist in a variety of distinct solid forms, having each of them unique physiochemical properties that influence the bioavailability, e.g. dissolution and absorption of the drug. All of these technical characteristics are critical for development of the final drug product.
In particular, for a pharmaceutical molecule to be “active” it has to reach it site of action in the body. Most often the molecules are not directly “bioavailable”, and are thus not directly absorbed in the body. In order to be absorbed, the molecules have to show adequate solubility and dissolution rates.
Dissolution of the molecule usually takes place in the stomach (for oral dosage forms), whereas the absorption takes place in the intestines. In the stomach the pH is quite low (varying from 1 to 5 depending on the individual), i.e. the initial dissolution takes place in a quite acidic environment. As many pharmaceutical products are either acids or bases it implies that the solubility/dissolution thereof is very dependant on the pH, so when evaluating the bioavailability of drugs pH dissolution values plays a crucial role.
Pirlindole, 2,3,3a,4,5,6-hexahydro-1H-8-methyl-pyrazine [3,2,1-j,k]carbazole, is a tetracyclic compound well known in medicine as being a reversible monoamine oxidase A inhibitor, useful as a medicament in the treatment of depression.
Further, pirlindole has also been shown to be useful for the treatment of diseases characterized by hyperproliferation of keratinocytes and/or T cells, in particular psoriasis and neurodermatisitis, as described in United States Patent Application US 2008/0254106.
Pirlindole pharmaceutically active forms include the mesylate and hydrochloride salts thereof.
However, therapeutic treatment methods with pirlindole have shown that there still exists field of improvement as regards the provision of alternative forms of the parent compound pirlindole which show an improved dissolution rate and solubility rate adequate for drug developing purposes.
The present invention therefore provides new, alternative and stable forms of pirlindole showing unexpectedly superior dissolution rates in acid environment, which result in increased absorption rates of the said active ingredient and thus are specially suitable to be used in medicine.